Goal. The long term objective of this project is to improve the safety and efficacy of percutaneous balloon angioplasty by establishing a scientific basis for determining the optimal dilation method based on measurements of the mechanical behavior atherosclerotic lesions. Background. At present, due to lack of direct evidence for the mechanism of angioplasty, balloon dilation methods vary widely, and conflicting approaches to choosing the rate, maximum distension, duration, and frequency of inflations are advocated by experienced operators. As a result, patients may not be receiving maximal benefit of the procedure. Specific Aims. The immediate aim of this study is to determine the optimal method for balloon dilation by systematically testing the influence of inflation characteristics on dilation results in atherosclerotic arteries, then applying these findings to prospective studies. Rationale. Effective dilation of a given arterial lesion requires permanent physical alteration which, in turn, requires that it be stretched beyond its elastic limit. Safe dilation requires that any plaque disruption occur in a "safety-glass" pattern, consisting of micro-fractures rather than single, large tears which lead to dissection. The strain rate required to achieve this effect and the elastic limit for atherosclerotic arteries are not known. These and other factors affecting response to dilation can be assessed in vivo in using a novel method based on measurement of the pressure-volume relation of the lesion via the catheter. Design. Four stages will be used: (1) validation of the method of pressure-volume monitoring in excised, superfused arteries and in vivo, (2) determination of the effect of atherosclerosis on arterial properties, (3) identification of the optimum inflation method(s) for in vitro arteries as a function of the type and severity of atherosclerotic lesion, and (4) application of the optimal in vitro method to identify optimal inflation protocol. Mechanical behavior will be assessed in terms of passive and active visco-elastic parameters. Optimum outcome will be defined in terms of directly-measure pressure-flow and pressure-volume relations for in vitro studies and in terms of quantitative-arteriographically determined pressure-flow relations. Lesions will be classified according to gross and microscopic pathologic characteristics. Significance. This study has immediate applications to treatment of atherosclerotic vascular disease, and findings may contribute to knowledge of the mechanism of balloon angioplasty. The effect of diffuse atherosclerosis on coronary flow dynamics, and the effect of active arterial tone on angioplasty outcome.